344 27 JANUARY 2017 • VOL 355 ISSUE 6323 sciencemag.org SCIENCErodents over to colleagues at USC, who killthe animals and check their brains for signsof neurodegeneration.

Caleb Finch and Todd Morgan, USC neuroscientists who combine studies of aging and
the brain, are in charge of the analysis. In
mice that breathed the dirty air, they have
found, the brain’s microglia release a flood
of inflammatory molecules, including tumor
necrosis factor a, which is elevated in the
brains of people with Alzheimer’s disease
and has been linked to memory loss. The
pollution-exposed mice also showed other
signs of brain damage, the group has reported in several recent papers: more amyloid b than in the control mice and shrunken
and atrophied neurites, the cellular processes
that extend from neurons toward other cells.

Just how the fine airborne particles mighttravel from a rodent’s nasal cavity to itsbrain is a mystery. But a research team ledby Günter Oberdörster at the University ofRochester in New York has used traceable,radioactive specks of elemental carbon todemonstrate that inhaled particles smallerthan 200 nanometers can get through thedelicate tissues lining a rodent’s nasal cavi-ties, travel along neurons, and spread as faras the cerebellum, at the back of the brain,triggering an inflammatory reaction.

To understand what the animal studies
might mean for people, however, scientists
need to correlate air pollution exposure with
human brain scans and with results from
rigorous cognitive testing.

That’s not easy to do, as long-term, historical data on pollution exposures are scarce in
the United States and many other countries,
says Kimberly Gray, a program administrator
at the National Institute of Environmental
Health Sciences (NIEHS) in Durham, North
Carolina. But in a September 2016 review of

18 epidemiological studies from Taiwan, Sweden, Germany, China, the United Kingdom,
and the United States, all but one showed
an association between high exposure to at
least one component of air pollution and a
sign of dementia. The review, published in
Neurotoxicology, included a 2012 analysis of 19,000 retired U.S. nurses, which
found that the more fine particulates the
nurses were exposed to, based on monitoring data near their homes, the faster they
declined on cognitive tests. For every additional 10 micrograms per cubic meter of air
they breathed, their performance on tests
of memory and attention declined as if they
had aged by 2 years, says Jennifer Weuve, an
epidemiologist at Boston University, who led
the analysis.

Imaging studies also suggest that pollution attacks the human brain. In a 2015 analysis of brain MRI scans of people enrolled
in the Framingham Heart Study, a long-term
cardiovascular study in New England, researchers at Harvard Medical School in Boston found that the closer people had lived to
a major roadway—and thus the more PM2.5
they had likely been exposed to—the smaller
their cerebral brain volume. The association
held up even after adjusting for factors such
as education, smoking, diabetes, and cardiovascular disease.

Shortly after that study was published,
USC’s Chen reported another example of
brain shrinkage: In 1403 elderly women, the
total volume of white matter—the insulated
nerve fibers that connect different brain
regions—decreased by about 6 cubic centimeters for every 3.5-µg/m3 increase in estimated PM2.5 exposure, based on air monitoring data from participants’ residences for
6 to 7 years before the brain scans were taken.
Chen’s white matter findings are consistent
with studies of cultured neurons, which
show that exposure to PM2.5 can cause
myelin—the fatty insulation that wraps
around neuronal axons—to “peel up at the
ends, like a Band-Aid,” Block says.

WHERE THE RISK IS GREATEST is far from
clear. Burning just about anything produces
PM2.5: oil and gas, firewood, vegetation.
Federal- and state-funded networks of air
quality monitors in the United States get
turned off and on according to political
whim, and are frustratingly uneven. According to the American Lung Association less
than a third of U.S. counties have ozone or
particle pollution monitors, and coverage is
especially sparse in rural areas. Those that
exist have only measured PM2.5 since 1997—
before that, EPA did not monitor particles
smaller than PM10.

Over the past several years, however, newcomputational models have made it possible

Adverse brainefects

Lung

Cytokines

3

2

PM10

(10 ;m)

PM2.5

(2.5 ;m)

60 ;m1 ;mFossil fuelsAshPollutantsIndustrial waste

Olfactory bulb

1

Human
hair

Modes of attack

Pollutant particles might make their way to the brain and
damage it directly, or they might attack it from a distance,
by triggering the release of inflammatory molecules.

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Beyond fine

Pollutant particles are classified and
regulated by size, although “ultrafine”
pollutants of about 0.2 µm are
unregulated. The smaller the particle,
the more damage it may do the brain.

Olfactory bulb transmission

Particles may enter the
nose and travel through the
olfactory bulb into the brain,
directly seeding plaques
and causing other problems.

Nasal epithelial transmission

Particles may affect the lining of
the nasal epithelium, producing
inflammation that damages
the brain.